This revised application is for a Mentored Faculty Development Award to prepare Dr. Mercedes Becerra for a successful career as an independent investigator in tuberculosis epidemiology. Dr. Becerra completed a doctoral program in epidemiology at the Harvard School of Public Health and is currently Assistant Professor in the Department of Social Medicine of the Harvard Medical School. She now proposes a five-year training and research program that will consist of additional specialized training and an intensive research experience under the guidance of Dr. Eric J. Rubin as the Research Mentor; Dr. Howard Hiatt as the Career Development Mentor; and an Advisory Committee of experts in epidemiology, biostatistics, social medicine, immunology, and molecular genetics. The mentored project will be linked to ongoing research activities of the team of advisors. Tuberculosis is a leading cause of morbidity and mortality, and the emergence of multidrug-resistant (MDR) strains of M. tuberculosis threatens global tuberculosis control because these strains are much more difficult and expensive to treat than drug-sensitive strains. The candidate will test the hypothesis that mutations found in transmitted MDR M. tuberculosis are likely to be those associated with minimal fitness costs when compared to those found in MDR strains that are not transmitted. Specific aims are: (1) To measure the association between specific resistance-conferring mutations in M. tuberculosis and the occurrence of secondary cases in household contacts. (2) To assess the impact of other mutations in M. tuberculosis, and clinical and demographic characteristics, on these associations. The candidate will achieve these aims by conducting a case-control study nested in a clinical cohort of over 1,000 patients with pulmonary MDR tuberculosis in Peru, where she has developed productive collaborations. At the end of the grant period, the candidate will have gained substantial experience in the inclusion and analysis of molecular-genetic data in the methodologically rigorous study of the natural history and epidemiology of drug-resistant tuberculosis. The cumulative effect of this award will be to enable Dr. Becerra to compete successfully for NIH individual investigator funding and maximize her potential to pursue an academic career as a tuberculosis epidemiologist.